Sex differences and adverse drug reactions

Not everybody responds to medication in the same way. Many don’t get a benefit, and some get adverse effects. As we start to understand the genetic differences between in drug response, hope exists that we can more clearly predict these outcomes from the genotype of individuals. This future is starting to arrive, but not at an even pace in different therapeutic areas. Sometimes, more simplistic broad categorisations can be used.

One of those is sex. Women are more at risk of some forms of adverse drug reactions. Amongst other things, women may have a lower lean body mass (but be given the same standard dose as a man), have differences in the drug metabolising cytochrome P450 enzymes, and be more at risk of QT elongation (a cardiac condition, that can lead to your heart beating dangerously fast).

A new paper by Ekhart et al (2018) examined 6791 spontaneously reported suspected adverse drug reactions of selective serotonin reuptake inhibitors (SSRIs – a group of anti-depressants) for men and women in the Lareb database of the Netherlands. They found:

68% of reports concerned women.

The percentage of serious reports 31.6% for men and 22.9% for women.

16 adverse drug reactions were more likely to be reported in women.

4 adverse drug reactions were more likely to be reported in men.

Women and men received the same doses of SSRIs (exception: men received higher a dose of citalopram)

The adverse reactions with differences are below.

The authors note that many of these differences may be due to pharmacokinetic sex differences. Greater absorption of the drug in women and lower metabolism of the drugs, leading to higher drug concentrations. This would in turn make dose-related adverse drug reactions more likely. However, some of the differences could be due to the seriousness of a particular adverse drug reaction being viewed differently. For example, hair loss (alopecia) may be reported less frequently by men.

There are large caveats on this data. Spontaneously reported data cannot provide definitive evidence, due both to the differential reporting and the wider under-reporting seen. Spontaneous adverse drug reactions are also suspected, not proven. However, it is worth noting specific differences that might heighten your ability to notice a problem, and the general point that the standard doses are likely to produce higher drug concentrations in women, in turn leading to more more risk of a adverse drug reaction.

Like all broad assumptions based on a group identity, the specific is always more important. Pay attention to the needs of the individual in front of you. Group differences are group differences, not predictions for individuals.